For most individuals who suffer from gallstones, the treatment of choice is to have a cholecystectomy, or surgical removal of the gallbladder. Each year 500,000 such operations are done in the United States alone. Recently, because of the cost, prolonged recuperation time and possible side effects associated with this surgery, methods have been developed for chemically removing gallstones in situ. Generally, this procedure involves inserting a catheter into the gallbladder followed by infusing a chemical solvent capable of dissolving the gallstone. The procedure thus avoids the need for and attendant risk of surgery.
A variety of chemical solvents have been tried and found to exhibit varying efficiencies of gallstone dissolution, depending on the chemical nature of the gallstone. Gallstones are generally composed of cholesterol or calcium salts, particularly calcium bilirubinate and calcium carbonate. Lipid solvents are effective at dissolving cholesterol gallstones, whereas these solvents have little or no solubilizing effect on gallstones composed of calcium salts. Thus, diethyl ether readily dissolves cholesterol gallstones, and other solvents such as mono-octanoin, and octadiol (glyceryl-1-octyl ether) also have good solubilizing properties. Unfortunately, few if any solvents are satisfactory for dissolving calcium gallstones. The invention herein will therefore find principal utility in cholesterol gallstone removal. It has been recognized that ether compounds such as diethylether have excellent cholesterol solubilizing properties, low viscosity and very good kinetic solubility but diethylether is hazardous since it boils below body temperature. Recently methyl tert-butyl ether (MTBE), a solvent hithertofore used primarily as a gasoline additive and a chromatographic solvent media, has been used for gallstone dissolution since it exhibits all the properties of ethers. Moreover, MTBE boils above body temperature and the solvent rapidly dissolves the gallstones without damaging the mucosa of the gallbladder.
The effectiveness of such new solvents has led to considerable activity focused on developing apparatus and methods for delivering MTBE and similar solvents to patients suffering from gallstones in ways to most rapidly and effectively solubilize gallstones without the complications arising from introducing such solvents into the body. (For brevity herein, the description will be with respect to use of the MTBE as a solvent. It will be recognized, however, that this invention will be applicable to a number of different solvents).
Physicians currently treat cholesterol gallstones by infusing MTBE into the gallbladder through a percutaneously positioned catheter through which MTBE is manually passed using glass syringes [Walker, Lancet, 1, 874 (1891); Shortsleeve, Radiology, 153, 547 (1984); and Teplick, Radiology, 153, 379 (1984)]. Additionally, physicians have available fixed volume syringe pumps, such as described in U.S. Pat. No. 4,655,744 to Thistle et al. to infuse and aspirate MTBE. There are several complications associated with either the manual infusion or the fixed volume pump-assisted infusion procedure.
When MTBE is delivered manually via glass syringes or with the aid of a fixed volume-cycle pump, spontaneous gallbladder contraction or over filling of the gallbladder cannot be detected or controlled. Consequently, MTBE periodically empties into the duodenum, producing duodenal mucosal injury, which in turn produces nausea, vomiting, duodenal erosions and accompanying pain of sufficient intensity to necessitate frequent administration of analgesics. In addition, when in the duodenum, MTBE can be absorbed into the blood stream, which in turn may result in somnolence or hemolysis and concomitantly the presence of the intense and irritating MTBE odor in the patient's breath.
Other problems associated with the manual or pump-associated syringe method involve inefficient removal of insoluble gallstone particles which constitute varying percentages of cholesterol gallstones. Such particles are often left behind in the gallbladder, after MTBE dissolves the cholesterol portion, in procedures involving syringes or syringe pumps. These particles often serve as the nidus for new gallstone formation. Additionally, both procedures are time consuming, laborious and require individuals that are highly skilled in their use. Consequently, the procedures are expensive because of the attendant costs associated with having a highly skilled staff of professional people to perform the procedure for prolonged times, often 12 hours or more. In addition, a fixed volume syringe pump can not prevent bile from entering the gallbladder during the course of its secretion by the liver. Bile in the gallbladder impedes the solvent's contact with stones and hence delays the process of dissolution.
It is obvious that delivering MTBE to a patient requires the utmost care to avoid releasing the solvent into the patient's bodily fluids or outside the area of treatment. Thus a key consideration in developing devices used in the chemical therapy of gallstone dissolution is ensuring the controlled delivery and removal of the solvent used to dissolve the gallstones. Considering that studies have shown that solvents such as MTBE are injurious if they pass into the intestine where they get absorbed, there is a critical need for devices that ensure that such chemicals will not be released during chemical therapy for gallstone removal. At the same time such devices must be able to maintain high solvent circulation rates into the gallbladder to create the necessary turbulence that will enhance dissolution and aid in evacuating the insoluble residue.
Also, because of the need to ensure containment of solvents, in addition to the safety features described above, a suitable device should be "user friendly" and not require the presence of highly skilled technicians to run the device. Further, for the same reasons, it should be easily maintainable.
With a little reflection, it becomes apparent that there are considerable hurdles to surmount if one is to develop a device that has the features described above. For instance, it must be "intelligent" and capable of sensing instantaneous changes in gallbladder pressure brought about by gallbladder contractions or by infusing the solvent, and rapidly relay this information to controlling feedback circuits. This is a crucial feature for such a device. If a gallstone should in some way prevent the necessary circulation of the solvent through the gallbladder, a critical pressure will build up, possibly rupturing the organ or causing leakage of the solvent from the gallbladder through the cystic duct into the common duct and intestine. Thus the device must be "intelligent" in the sense that it senses gallbladder pressure changes over a predefined range and reacts fast enough to keep the pressure in that range, shutting down or reacting appropriately if the pressure persists outside the range. Moreover, it would be desirable to have a device that not only is capable of shutting down, but actually can flush out any debris causing the blockage, and resume normal operation should the debris be removed. Such device should prevent intra-gallbladder pressure from rising above leakage limit and from falling below the pressure under which bile will be sucked into the gallbladder from the biliary duct.